Abstract Cancer cells employ bidirectional cell communication to maintain growth and metastasis in the tumor microenvironment. One mechanism of communication that has become increasingly appreciated is the secretion of extracellular vesicles (EVs), heterogeneous multi-signal messengers that support cancer dissemination through the transfer of biomolecules such as oncoproteins and noncoding RNA species. However, little is understood about EVs in relation to chemotherapy resistance. In this study, we profiled two different breast cancer cell lines: 1) BT549 (triple negative), treated with gemcitabine and paclitaxel chemotherapy, and 2) MCF7 (estrogen receptor-positive), treated with palbociclib and fulvestrant, compared to their wild-type states. EVs were collected from these cells using tangential flow filtration and quantified with Brownian motion-based nanoparticle tracking analysis and microfluidic resistive pulse sensing, and profiling of RNA and peptide markers was completed through RT-qPCR and Western blotting, respectively. Initial data showed that representative mitochondrial ribosomal genes mt12S and MRPS14 were among the most upregulated RNAs in our drug-exposed EV samples, indicating that extracellular transfer of mitochondrial materials plays a role in cancer growth under chemotherapy stress. These findings were supported by prior genetic research at the Vasudevan laboratory, in which a set of mitochondrial ribosomal RNAs was found to be upregulated in cytosine arabinoside-induced chemoresistant acute monocytic leukemia cells, as well as by the recent discovery of mitovesicles, a novel population of EVs that originate from mitochondria. Through additional efforts to isolate further subtypes of EVs, the mechanisms by which these mitochondrial cargoes promote chemoresistant phenotypes will be uncovered. Citation Format: Harrison Ngue, Hyejin Kim, Shobha Vasudevan. Characterizing cargoes of extracellular vesicles in promoting breast cancer growth and chemotherapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5829.
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